A gene variant present in about 50 percent of the global population that is known to contribute to obesity is now believed to be associated with yet another dire effect: significant brain tissue loss.
Three years ago, researchers determined that the FTO gene variant, or allele, was associated with obesity.
Now, UCLA scientists have also discovered that those with the FTO allele also have 8 to 12 percent less tissue in certain areas of the brain.
By analyzing 206 MRI brain scans of elderly subjects, researchers at UCLA’s Laboratory of Neuro Imaging found less tissue in the frontal and occipital lobes, which control higher thinking skills and visual processing, respectively.
The FTO allele is all too common. Forty-six percent of people of European descent and 25 percent of Hispanics carry the variant. Twenty percent of African Americans and Asian Americans carry the FTO allele, too.
“It is a fairly worrying finding. No one would believe that such a common variant would have such a big impact,” said Dr. Paul Thompson, UCLA professor of neurology and senior study author of the paper published last week in the journal Proceedings of the National Academy of Sciences.
But a person who has the gene variant is not guaranteed to become obese or suffer from above average tissue loss.
“Even if one is predisposed to weight gain and brain loss, it does not mean that he will get a disease or be obese,” said Jason Stein, a third-year graduate student and a lead author.
A carrier is simply more likely to see these changes in brain and body composition, he added.
There are also ways to reduce the effects of the gene on one’s body and brain, Thompson said.
“If it is such a severe hit to the brain, there are a lot of things we could do to basically combat the effect of this gene,” he said. “Exercise, a low-fat diet and mind-stimulating education all help.”
Further experiments that were carried out to determine how the gene operates in the body could potentially result in drugs and treatments for various weight conditions and degenerative disorders, such as Alzheimer’s disease, Thompson said.
“Drug companies are working very hard to combat the effects of the gene,” he said. “If they do, (they would) have a gold mine for treating obesity and dementia.”
The FTO allele is clearly associated with both brain damage and obesity, but the connection between the two effects remains vague, Thompson said.
Three years ago, researchers based in Pittsburgh began studying more than 35,000 subjects around the world and determined that, on average, FTO carriers have half-inch larger waistlines and weigh an extra 3 to 7 pounds compared to those lacking the gene variant.
“It may be that the gene makes you want to eat more, the fat starts to clump up your heart, and blood flow into your brain is reduced,” Thompson said. “Or maybe the protein made by the gene is damaging the brain directly.”
In order to determine why this connection exists, researchers must identify what happens once the gene is expressed, said April Ho, a third-year graduate student and a lead author.
The brain maps pointed out areas of reduced volume in the brain, but MRIs only detect structural differences, not mechanistic ones.
“This is only the first step in helping to tell us how (the allele) affects our functioning and thinking,” Ho said.